Melanomas are aggressive, frequently metastatic tumors derived from either melanocytes or melanocyte related nevus cells (“Cellular and Molecular Immunology” (1991) (eds) Abbas A. K., Lechtman, A. H., Pober, J. S.; W. B. Saunders Company, Philadelphia: pages 340-341). According to the American Cancer Society, melanomas make up approximately three percent of all skin cancers but cause most skin cancer-related deaths, and the incidence rate for melanoma (number of new cases of melanoma per 100,000 people each year) has more than doubled since 1973. While the mortality rate for melanoma has increased at a slower pace, there is an ongoing need to develop new melanoma therapies.
Like many cancers, melanomas are believed to arise at least in part because of unresponsiveness to self-tumor antigens which prevents the immune system from eliminating cancerous cells. One technique that has been investigated to overcome such unresponsiveness is the use of antigen mimics. Various types of tumor antigen mimics have been identified. Among them, the most extensively utilized antigen mimics are anti-idiotypic antibodies (anti-Id-Abs), which have been developed in several human tumor antigen systems (for review, see Wang, et al. (2001) Cancer Chemother. Biol. Response Modif. 19, 309-326).
Anti-id mAbs markedly differ in their immunogenicity as measured by their ability to elicit a humoral immune response to the corresponding self-tumor antigen. However, the cause of this variability is not known. This lack of information reflects the limited knowledge about the structural basis of antigen mimicry by anti-id antibodies and about the ability of a mimic to overcome unresponsiveness to a self-tumor antigen.
For example, an anti-id mAb (MK2-23) has been developed against a melanoma antigen (Kusama et al. (1989) J. Immunol. 143, 3844-3852). However, little is known about the molecular mimicry of the antigen by this anti-id mA. This lack of information has precluded further development of compositions based on this mimicry for use in stimulating an immune response to melanomas. Therefore, there is a need to analyze the molecular basis of melanoma antigen mimicry by this anti-id mAb and to develop compositions based on the analysis for use in stimulating an immune response to melanoma.